Contribution of plasma membrane Ca²⁺ATPase to cerebellar synapse function

Abstract

The cerebellum expresses one of the highest levels of the plasma membrane Ca 2+ ATPase, isoform 2 in the mammalian brain. This highly efficient plasma membrane calcium transporter protein is enriched within the main output neurons of the cerebellar cortex; i.e. the Purkinje neurons (PNs). Here we review recent evidence, including electrophysiological and calcium imaging approaches using the plasma membrane calcium ATPase 2 (PMCA2) knockout mouse, to show that PMCA2 is critical for the physiological control of calcium at cerebellar synapses and cerebellar dependent behaviour. These studies have also revealed that deletion of PMCA2 throughout cerebellar development in the PMCA2 knockout mouse leads to permanent signalling and morphological alterations in the PN dendrites. Whilst these findings highlight the importance of PMCA2 during cerebellar synapse function and development, they also reveal some limitations in the use of the PMCA2 knockout mouse and the need for additional experimental approaches including cell-specific and reversible manipulation of PMCAs. THE CEREBELLUM, THE PURKINJE NEURON AND THE IMPORTANCE OF CALCIUM DYNAMICS AT CEREBELLAR SYNAPSESThe cerebellum is a major centre for the integration of sensory and motor information in the brain and plays a central role in our ability to learn and refine motor tasks; the specialised function of the cerebellum allows us to execute motor tasks in a finely controlled but, at the same time, "unaware" manner that can still be improved by learning. For a detailed review of cerebellar function TOPIC HIGHLIGHTWorld J Biol Chem 2010 May 26; 1(5): 95-102 ISSN 1949-8454 (online)

Carbonic Anhydrase 8 Expression in Purkinje Cells Is Controlled by PKCγ Activity and Regulates Purkinje Cell Dendritic Growth

“…Blockade of voltage-gated calcium channels could partially protect Purkinje dendrite cells from the stunted growth seen with increased PKC activity [5], and Purkinje cells from Moonwalker (Mwk) mutant mice with increased calcium influx through TRPC3 channels also show a stunted dendritic morphology [6]. Similarly, inhibition of the plasma membrane calcium-ATPase 2 (PMCA2) affected Purkinje cell dendritic growth [7,8]. These findings demonstrate the involvement of the calcium equilibrium for regulating Purkinje cell dendritic growth, but still very little is known about the downstream molecular interactions after PKC activation in Purkinje cells leading to the reduced dendritic growth.…”

Anthocyanins restore behavioral and biochemical changes caused by streptozotocin-induced sporadic dementia of Alzheimer's type

“…The former enzyme is responsible for the active transport of Na + and K + , and it is necessary to maintain the ionic gradient across membranes and thus it is essential to regulate neuronal excitability A C C E P T E D M A N U S C R I P T (Jimenez, Sanchez, 2010, Jorgensen et al , 2003, Kaplan, 2002. The Ca 2+ -ATPase is one of the most powerful modulators of intracellular Ca 2+ levels (Casteels et al , 1991, Huang et al , 2010, Raeymaekers and Wuytack, 1991.…”

“…The transient changes in intracellular Ca 2+ levels regulate a wide variety of cellular processes and cells employ both intracellular and extracellular sources of Ca 2+ for the activation of signaling pathways and regulation of many physiological and pathological processes (Huang, Nagaraja, 2010, Missiaen et al , 2000a, Missiaen et al , 2000b, Ruknudin and Lakatta, 2007).…”

Changes in activity of hippocampus creatine kinase under circadian rhythm disorders

“…Calcium levels were increased in both the mitochondrial and cytosolic fractions under stress conditions (Figure 3a). Since Ca 2+ -ATPase is one of the systems affecting the content of calcium ions in cell (Delivoria-Papadopoulos et al 2008;Huang et al 2010), our next step was to determine the change in Ca 2+ -ATPase activity in the hippocampal cells of the stressed animals. The results are shown in In addition, quantitaive changes of NO levels in the cells of the hippocampus were studied.…”